Du YiHeng, Sui YiQun, Cao Jin, Jiang Xiang, Wang Yi, Yu Jiang, Wang Bo, Wang XiZhi, Xue BoXin
Department of Urology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou, China.
Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Front Cell Dev Biol. 2022 Mar 2;10:833578. doi: 10.3389/fcell.2022.833578. eCollection 2022.
Bladder cancer (BLCA) is a tumor that possesses significant heterogeneity, and the tumor microenvironment (TME) plays an important role in the development of BLCA. The TME chiefly consists of tumor cells and tumor-infiltrating immune cells admixed with stromal components. Recent studies have revealed that stromal components, especially cancer-associated fibroblasts (CAFs), affect immune cell infiltration and modulate the extracellular matrix in the TME of BLCA, ultimately impacting the prognosis and therapeutic efficacy of BLCA. Among the subgroups of CAFs, myofibroblasts (myCAFs) were the most abundant and were demonstrated to play an essential role in affecting the prognosis of various tumors, including BLCA. However, the dynamic changes in myCAFs during carcinogenesis and tumor progression have been less discussed previously. With the help of bioinformatics algorithms, we discussed the roles of myCAFs in the carcinogenesis and prognosis of BLCA in this manuscript. Our study highlighted the pathogenesis of BLCA was accompanied by a decrease in the abundance of myCAFs, revealing potential protective properties of myCAFs in the carcinogenesis of BLCA. Meanwhile, the reduced expressions of myCAFs marker genes were highly accurate in predicting tumorigenesis. In contrast, we also demonstrated that myCAFs regulated extracellular matrix remodeling, tumor metabolism, cancer stemness, and oncological mutations, ultimately impacting the treatment responsiveness and prognosis of BLCA patients. Thus, our research revealed the bimodal roles of myCAFs in the development of BLCA, which may be associated with the temporal change of the TME. The in-depth study of myofibroblasts and the TME may provide potential diagnostic biomarkers and therapeutic targets for BLCA.
膀胱癌（BLCA）是一种具有显著异质性的肿瘤，肿瘤微环境（TME）在BLCA的发展中起着重要作用。TME主要由肿瘤细胞和与基质成分混合的肿瘤浸润免疫细胞组成。最近的研究表明，基质成分，尤其是癌症相关成纤维细胞（CAFs），会影响免疫细胞浸润并调节BLCA的TME中的细胞外基质，最终影响BLCA的预后和治疗效果。在CAFs的亚组中，肌成纤维细胞（myCAFs）最为丰富，并被证明在影响包括BLCA在内的各种肿瘤的预后中起重要作用。然而，之前较少讨论myCAFs在致癌过程和肿瘤进展中的动态变化。借助生物信息学算法，我们在本手稿中讨论了myCAFs在BLCA致癌作用和预后中的作用。我们的研究强调BLCA的发病机制伴随着myCAFs丰度的降低，揭示了myCAFs在BLCA致癌过程中的潜在保护特性。同时，myCAFs标记基因的表达降低在预测肿瘤发生方面具有高度准确性。相比之下，我们还证明myCAFs调节细胞外基质重塑、肿瘤代谢、癌症干性和肿瘤突变，最终影响BLCA患者的治疗反应性和预后。因此，我们的研究揭示了myCAFs在BLCA发展中的双重作用，这可能与TME的时间变化有关。对肌成纤维细胞和TME的深入研究可能为BLCA提供潜在的诊断生物标志物和治疗靶点。
